ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2011
Mathematical modeling predicts the effect of folate deficiency and excess on cancer-related biomarkers.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Pro-Carcinogenic Implications of Folic Acid Supplementation During Chemically Induced Cutaneous Squamous Cell Carcinoma in Mice.Journal of biochemical and molecular toxicology · 2026Article
- Integration of scRNA and bulk RNA-sequence to construct the 5-gene molecular prognostic model based on the heterogeneity of thyroid carcinoma endothelial cell.Acta biochimica et biophysica Sinica · 2024Article
- The Evolving Role of Multivitamin/Multimineral Supplement Use among Adults in the Age of Personalized Nutrition.Nutrients · 2018Review
- Improvement of gamete quality by stimulating and feeding the endogenous antioxidant system: mechanisms, clinical results, insights on gene-environment interactions and the role of diet.Journal of assisted reproduction and genetics · 2016Review
- Bacterial Folates Provide an Exogenous Signal for C. elegans Germline Stem Cell Proliferation.Developmental cell · 2016Article
- Red blood cell folate and plasma folate are not associated with risk of incident colorectal cancer in the Women's Health Initiative observational study.International journal of cancer · 2015Observational
- Lower serum folate is associated with development and invasiveness of gastric cancer.World journal of gastroenterology · 2014Article
- Article
- Folate metabolite profiling of different cell types and embryos suggests variation in folate one-carbon metabolism, including developmental changes in human embryonic brain.Molecular and cellular biochemistry · 2013Article
- Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence on prostate cancer risk and interactions.Frontiers in oncology · 2012Article
- Article
- Dietary factors and epigenetic regulation for prostate cancer prevention.Advances in nutrition (Bethesda, Md.) · 2011Review
- Modeling cellular compartmentation in one-carbon metabolism.Wiley interdisciplinary reviews. Systems biology and medicineReview
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundFolate is an essential B-vitamin that mediates one-carbon metabolism reactions, including nucleotide synthesis and others related to carcinogenesis. Both low- and high-folate status influences carcinogenesis.
methodsWe used a mathematical model of folate-mediated one-carbon metabolism to predict the effect of a range of intracellular epithelial folate concentrations (0.25-15.0 μmol/L) on methylation rate and purine and thymidylate synthesis. We also examined the interaction of these folate concentrations with polymorphisms in two enzymes [methylene tetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS)] in relation to the biochemical products.
resultsTS enzyme reaction rate increased markedly in response to the modeled higher intracellular folate concentrations. Changes in methylation rate were modest, whereas purine synthesis was only minimally related to increases in folate concentrations with an apparent threshold effect at 5.0 to 6.0 μmol/L. The relationship between folate concentrations and thymidylate synthesis was modified by genetic variation in TS but less so by variation in MTHFR. These gene-folate interactions modestly influenced purine synthesis in a nonlinear manner but only affected methylation rate under conditions of very high MTHFR activity.
conclusionThymidylate synthesis is very sensitive to changes in epithelial intracellular folate and increased nearly fivefold under conditions of high intracellular folate. Individuals with genetic variations causing reduced TS activity may present even greater susceptibility to excessive folate. IMPACT: Our observation that thymidylate synthesis increases dramatically under conditions of very elevated intracellular folate provides biological support to observations that excessive folic acid intake increases risk of both precursor lesions (i.e., colorectal adenomas) and cancer.
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